1. Field of the Invention
This invention relates to a method of producing the nicotinyl ester of 6-aminonicotinic acid. More particularly, the invention relates to a method of producing such ester in high yield.
2. Description of the Prior Art
U.S. Pat. No. 4,141,977, issued Feb. 2, 1979 to Eugene Van Scott and Ruey J. Yu, discloses 6-substituted nicotinic acid and its esters when topically applied are useful in alleviating the symptoms of psoriasis. The 6-aminonicotinic acid methyl ester, the ethyl ester, the tert. butyl ester and the nicotinyl ester are specifically disclosed. In col. 5, lines 59 et seq. of the patent, a method of synthesis of the ethyl ester is set forth. The method results in the production of an amount of 6-aminonicotinic acid ethyl ester corresponding to a yield of 82% based on the weight of the starting materials. One skilled in the art would appreciate that if this method were utilized to produce the nicotinyl ester, a substantially lower, unacceptable, yield would result.
U.S. Pat. No. 2,199,839, issued May 7, 1940 to Raemer R. Renshaw and Paul F. Dreisbach, also discloses the synthesis of a variety of lower alkyl esters of 6-aminonicotinic acid by the method of Fischer esterification. Again, one skilled in the art would appreciate that a substantial yield of the nicotinyl ester of 6-aminonicotinic acid could not be obtained through use of this method. The hydrogen chloride gas would react with the nicotinyl alcohol to form an intractable mass. U.S. Pat. No. 2,199,839 further discloses reaction of the potassium salt of 6-aminonicotinic acid with 2-chloroethyldiethyl amine by heating both components on a steam bath in the absence of solvent. The present inventors similarly reacted the potassium salt of 6-aminonicotinic acid with 3-chloromethylpyridine. No yield whatsoever of nicotinyl ester of 6-aminonicotinic acid resulted. Only a tar was obtained.
Thus, there is need for development of a synthetic method for producing the nicotinyl ester of 6-aminonicotinic acid in high yield.